Aging is associated with marked declines in motor performance and cognitive function, and an increase in musculoskeletal disorder and pain, especially in women. The number of Americans >65 years in the workforce will more than double during the next 30 years so that older adults will comprise >25% of the workforce by 2050. Neuromuscular fatigue (exercise-induced loss of strength) and muscle pain that develops during low-intensity sustained postural contractions can be substantial and will increase risk of pain and injury during work-related tasks. To understand underlying factors that exacerbate fatigue with age, this proposal examines cognitive and genetic factors that contribute to greater neuromuscular fatigue and pain during static postural motor tasks of the upper limb especially in older women. We established that neuromuscular fatigability and loss of steadiness during low-intensity sustained upper limb contractions are greater for women than men when performing a challenging and stressful cognitive task. The impact of aging in older women is not known. This proposal therefore investigates the impact of age and sex on the impairment of motor performance and pain during a sustained postural fatiguing task when different levels of cognitive stress/demand are imposed. Importantly, Apolipoprotein-E e4 (APOE e4) allele inheritance conveys greater risk with increasing age of cognitive decline, and recently was associated with age-related reductions in strength. While neuromuscular fatigue exacerbates age-related decrements in strength in older adults and is likely more sensitive to APOE e4 inheritance, there are no studies addressing genetic inheritance and fatigue. This proposal also identifies whether APOE e4 contributes to differences in the magnitude of neuromuscular fatigue among older adults. Aim 1 will compare neuromuscular fatigue and pain during low-intensity postural fatiguing contractions of the upper limb in healthy young and older men and women in the presence and absence of a cognitive stressor. We hypothesize that older adults, especially women, will have greater changes in fatigue and pain when cognitive demand is increased compared with young adults. Aim 2 will determine whether the APOE e4 allele genotype is associated with age-related changes in neuromuscular fatigue and pain during low-intensity static fatiguing contractions among older men and women. We hypothesize that older adults who are APOE e4 allele carriers will exhibit the greatest fatigue and pain. This proposal adopts an innovative approach by identifying cognitive and genetic factors that predispose older adults to decrements in motor performance, increased fatigue and pain during sustained postural contractions. Identifying risk factors in older adults for motor decline will provide clinicians with a rationale to promote preventative interventions such as practice, or cognitive and physical training for sub-clinical populations before large motor function deficits occur, thus increasing productive and effective time in the work-force and more independent, healthy living in old age. PUBLIC HEALTH RELEVANCE: This proposal examines cognitive demand and genetic factors that can contribute to greater age-related neuromuscular fatigue and pain during static sustained postural fatiguing contractions of the upper limb. Sustained postural contractions are essential for daily and ergonomic tasks and increased neuromuscular fatigue place older women at greater risk of musculoskeletal injury and pain in an aging workforce. We target older adults who are genetically at risk of accelerated motor and cognitive decline (Apolipoprotein-E e4 allele positive) in order to identify healthy but subclinical older adults who are vulnerable to neuromuscular fatigue and pain when cognitive demand is imposed. The results will significantly impact treatment approaches to musculoskeletal disorders and pain and rehabilitation in an aging workforce.